Treatment of Burn Wounds with Chitosan and SEAL

Introduction

Burns sustained during military operations have an outsized impact since they are often very painful and potentially debilitating. Even burns to a small surface area can be incapacitating for the casualty.

Burn injuries may initially appear survivable but can progress into full-thickness wounds with marked edema, fluid loss, and infection. Particularly, concomitant soft-tissue injuries, such as those caused by blast, increase the risk of developing bacterial and/or fungal infections which may lead to morbidity and mortality. These complications may transform a potentially survivable injury into a fatal one. A rapid and effective intervention in the field will reduce the risk of deterioration which would result in disability and death [1-3].

The classical model for a burn comprises three concentric zones of injury: a central zone of necrosis, a surrounding zone of stasis, and a further zone of hyperemia surrounding the zone of stasis. The necrotic area is coagulated tissue that progresses to form an eschar. The hyperemic zone usually heals rapidly. The zone of stasis between these two zones may progress into full-thickness necrosis over 24-48 hours postburn. Therefore, maximizing salvage of the zone of stasis is of great importance in the management of burns [3], including immediate cooling which results in heat dissipation to decrease subdermal temperature [4].

Chitosan shows great potential in the management of burns due to its hemostatic, antimicrobial and wound healing properties. Chitosan powder applied on severe burns was found to reverse the process of early extension of the burn resulting in mild and superficial wounds in standardized animal experiments [5]. Due to its outstanding characteristics, chitosan may address severe complications associated with burn treatment, including bleeding, infection and scar formation [6].

Advantages of SEAL

SEAL developed by BC3 contains chitosan powder that can be applied to a burn immediately after the event. Because SEAL spray cools as it is released from the can, it will quickly reduce the heat from burned skin areas. In addition, the chitosan can remain bound to the wound surface as a protective antimicrobial layer in prolonged field care situations. Since burn wounds in combat are often caused by traumatic events, they may be associated with severe injuries and hemorrhage. In such cases, there will be a synergistic effect of SEAL which will combine an effective treatment of the bleeding and the burn.

Testing of SEAL in Swine Model of Severe Burn Injury

The efficacy and safety of SEAL to support the healing process of severe burn injuries was tested in a standardized model in swine. Full-thickness burn wounds were induced with a stainless steel device heated to 200±10°C according to a published procedure [7]. The wound healing was monitored for up to 60 days, with biopsies performed on days 14, 28, and 60. SEAL was compared with a standard collagen product marketed for treatment of burn wounds. In comparison to control, key outcomes of SEAL included:

• More organized healing: SEAL wounds looked more uniform with cleaner margins and fewer/ smaller necrotic crusts from day 14 onward.

• Earlier surface recovery: First signs of re-epithelialization appeared in SEAL by day 28 (none in controls at that point).

• Faster calming of inflammation: By day 60, SEAL showed lower residual polymorphonuclear neutrophils and macrophages, indicating quicker resolution of acute inflammation.

• Tissue quality trends: Slightly higher angiogenesis at day 60 and less fatty infiltrate at day 28 with SEAL, while fibrosis/scar maturation matched controls.

The figure provides representative examples of the wound healing process with SEAL vs. control:

In conclusion, SEAL supports a consistent, fast and efficiently progressing tissue regeneration and wound healing of severe burns.

The results were confirmed in a standardized full-thickness wound healing study in swine, which, due to the similar physical environment, mimics an excised burn wound. The wounds were largely epithelialized by day 14, and complete epithelialization of all wounds was observed by day 28.

References:

[1] Gurnay J et al., Burn injuries from a military perspective, Curr Trauma Rep 2022;8:113.

[2] Driscoll IR et al., Burn casualty care in the deployed setting, Mil Med 2018;183:161.

[3] Wright EH et al., Cooling of burns: Mechanisms and models, Burns 2015;41:882.

[4] Cuttle L et al., The optimal temperature of first aid treatment for partial thickness burn injuries, Wound Repair Regen 2008;16:626.

[5] Jin Y et al., Effects of chitosan and heparin on early extension of burns, Burns 2007;33:1027.

[6] Muzarelli R, Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone, Carbohydr Polym 2009;76:167.

[7] Blackstone BN et al., Scar formation following excisional and burn injuries in a red Duroc pig model, Wound Repair Regen 2017;25:618.